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Digestive Diseases and Sciences

, Volume 56, Issue 4, pp 1037–1046 | Cite as

5-Aminosalicylic Acid (5-ASA) Can Reduce Levels of Oxidative DNA Damage in Cells of Colonic Mucosa With and Without Fecal Stream

  • Caroline Caltabiano
  • Felipe Rodrigues Máximo
  • Ana Paula Pimentel Spadari
  • Daniel Duarte da Conceição Miranda
  • Marcia Milena Pivatto Serra
  • Marcelo Lima Ribeiro
  • Carlos Augusto Real Martinez
Original Article

Abstract

Background

No studies have evaluated the effectiveness of 5-ASA against oxidative DNA damage in experimental models of diversion colitis.

Aim

To evaluate the effects of 5-ASA against oxidative DNA damage in an experimental model of diversion colitis.

Methods

Twenty-six Wistar rats were divided into two groups corresponding to sacrifice at 2 or 4 weeks after fecal diversion of the left colon by means of proximal colostomy and distal mucosa fistula. Each group was divided into two subgroups according to intervention in excluded colon performed with 0.9% saline solution or 5-ASA. Level of oxidative DNA damage was determined by comet assay in cells obtained from segments with and without fecal stream before and after H2O2 challenge. For statistical analysis, was used one-way analysis of variance (ANOVA), adopting a 5% significance level (P < 0.05).

Results

Levels of DNA damage were always higher in colon segments without fecal stream, regardless of the intervention solution employed. DNA damage in colon segments with and without fecal stream in animals irrigated with 5-ASA was lower when compared with those treated with saline solution, regardless of time of irrigation. These levels remained lower after intervention with 5-ASA, even after H2O2 challenge.

Conclusions

Enema with 5-ASA reduces oxidative DNA damage in epithelial cells of colon segments without fecal stream, even after H2O2 challenge, confirming the effects of 5-ASA against DNA damage by oxygen free radicals.

Keywords

Colitis Mesalamine 5-Aminosalicylic acid Fatty acids Volatile Butyrates Rats 

Notes

Acknowledgments

C.A.R.M. thanks the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) for financial support. Process. N°. 2006/02306-6.

Financial support

Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), São Paulo, Brazil.

References

  1. 1.
    Glotzer DJ, Glick ME, Goldman H. Proctitis and colitis following diversion of fecal stream. Gastroenterology. 1981;80:438–441.PubMedGoogle Scholar
  2. 2.
    Bosshardt RT, Abel ME. Proctitis following fecal diversion. Dis Colon Rectum. 1984;27:605–607.PubMedCrossRefGoogle Scholar
  3. 3.
    Geraghty JM, Talbot IC. Diversion colitis: histological features in the colon and rectum after defunctioning colostomy. Gut. 1991;32:1020–1023.PubMedCrossRefGoogle Scholar
  4. 4.
    Lavoine E, Vissuzaine C, Cadiot G, et al. Proctitis of diversion on an excluded rectum in patients with hemorrhagic rectocolitis. Gastroenterol Clin Biol. 1996;20:243–247.PubMedGoogle Scholar
  5. 5.
    Haas PA, Haas GP. A critical evaluation of the Hartmann’s procedure. Am Sur. 1988;54:380–385.Google Scholar
  6. 6.
    Keli E, Bouchoucha M, Devroede G, et al. Diversion-related experimental colitis in rats. Dis Colon Rectum. 1997;40:222–228.PubMedCrossRefGoogle Scholar
  7. 7.
    Frisbie JH, Ahmed N, Hirano I, et al. Diversion colitis in patients with myelopathy: clinical, endoscopic, and histopathological findings. J Spinal Cord Med. 2000;23:142–149.PubMedGoogle Scholar
  8. 8.
    Bax TW, McNevin MS. The value of diverting loop ileostomy on the high-risk colon and rectal anastomosis. Am J Surg. 2007;193:585–587.PubMedCrossRefGoogle Scholar
  9. 9.
    Koutroubakis IE. Spectrum of non-inflammatory bowel disease and non-infectious colitis. World J Gastroenterol. 2008;14:7277–7279.PubMedCrossRefGoogle Scholar
  10. 10.
    Habr-Gama A, Teixeira MG, Vieira MJF, et al. Operaçäo de Hartmann e suas conseqüências. Rev Bras Coloproctol. 1997;17:5–10.Google Scholar
  11. 11.
    David GG, Al-Sarira AA, Willmott S, et al. Use of Hartmann’s procedure in England. Colorectal Dis. 2009;11:308–312.PubMedCrossRefGoogle Scholar
  12. 12.
    Curi A, Mascarenhas JCS, Moreira Junior H, et al. Morbimortalidade associada à reconstrução do trânsito intestinal—Análise de 67 casos. Rev Bras Coloproct. 2002;22:88–97.Google Scholar
  13. 13.
    Neut C, Guillemot F, Colombel JF. Nitrate-reducing bacteria in diversion colitis: a clue to inflammation? Dig Dis Sci. 1997;42:2577–2580.PubMedCrossRefGoogle Scholar
  14. 14.
    Villanacci V, Talbot IC, Rossi E, et al. Ischaemia: a pathogenetic clue in diversion colitis? Colorectal Dis. 2007;9:601–605.PubMedCrossRefGoogle Scholar
  15. 15.
    Roediger WE, Rae DA. Trophic effect of short chain fatty acids on mucosal handling of ions by the defunctioned colon. Br J Surg. 1982;69:23–25.PubMedCrossRefGoogle Scholar
  16. 16.
    Harig JM, Soergel KH, Komorowski RA, et al. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med. 1989;320:23–28.PubMedCrossRefGoogle Scholar
  17. 17.
    Neut C, Guillemot F, Gower-Rousseau C, et al. Treatment of diversion colitis with shorty-chain fatty acids. Bacteriological study. Gastroenterol Clin Biol. 1995;19:871–875.PubMedGoogle Scholar
  18. 18.
    Christl SU, Eisner HD, Dusel G, et al. Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa: a potential role for these agents in the pathogenesis of ulcerative colitis. Dig Dis Sci. 1996;41:2477–2481.PubMedCrossRefGoogle Scholar
  19. 19.
    Oliveira-Neto JP, Aguilar-Nascimento JE. Intraluminal irrigations with fibers improves mucosal inflammation and atrophy in diversion colitis. Nutrition. 2004;20:197–199.PubMedCrossRefGoogle Scholar
  20. 20.
    Scheppach W, Weiler F. The butyrate story: old wine in new bottles? Curr Opin Clin Nutr Metab Care. 2004;7:563–567.PubMedCrossRefGoogle Scholar
  21. 21.
    Wong JM, de Souza R, Kendall CW, et al. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol. 2006;40:235–243.PubMedCrossRefGoogle Scholar
  22. 22.
    Fillmann H, Kretzmann NA, San-Miguel B, et al. Glutamine inhibits over-expression of pro-inflammatory genes and down-regulates the nuclear factor kappaB pathway in an experimental model of colitis in the rat. Toxicology. 2007;236:217–226.PubMedCrossRefGoogle Scholar
  23. 23.
    Nassri CGG, Nassri AB, Favero E, et al. Influência da irrigação de soluções nutricionais no colo excluso de trânsito intestinal. Estudo experimental em ratos. Rev Bras Coloproct. 2008;28:306–314.Google Scholar
  24. 24.
    Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev. 2002;15:79–94.PubMedCrossRefGoogle Scholar
  25. 25.
    Pravda J. Radical induction theory of ulcerative colitis. World J Gastroenterol. 2005;11:2371–2384.PubMedGoogle Scholar
  26. 26.
    Nieto N, Torres MI, Ríos A, et al. Dietary polyunsaturated fatty acids improve histological and biochemical alterations in rats with experimental ulcerative colitis. J Nutr. 2002;132:11–19.PubMedGoogle Scholar
  27. 27.
    Roediger WE, Truelove SC. Method of preparing isolated colonic epithelial cells (colonocytes) for metabolic studies. Gut. 1979;20:484–488.PubMedCrossRefGoogle Scholar
  28. 28.
    Roediger WE. The starved colon—diminished mucosal nutrition, diminished absorption, and colitis. Dis Colon Rectum. 1990;33:858–862.PubMedCrossRefGoogle Scholar
  29. 29.
    Liu Q, Shimoyama T, Suzuki K, et al. Effect of sodium butyrate on reactive oxygen species generation by human neutrophils. Scand J Gastroenterol. 2001;36:744–750.PubMedCrossRefGoogle Scholar
  30. 30.
    Rosignoli P, Fabiani R, De Bartolomeu A, et al. Protective activity of butyrate on hydrogen peroxide-induced DNA damage in isolated human colonocytes and HT29 tumour cells. Carcinogenesis. 2001;22:1675–1680.PubMedCrossRefGoogle Scholar
  31. 31.
    Halliwell B, Gutteridge JM. Lipid peroxidation in brain homogenates: the role of iron and hydroxyl radicals. J Neurochem. 1997;69:1330–1331.PubMedCrossRefGoogle Scholar
  32. 32.
    Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Rad Biol Med. 2000;29:222–230.PubMedCrossRefGoogle Scholar
  33. 33.
    Gutteridge JM, Halliwell B. Free radicals and antioxidants in the year 2000. A historical look to the future. Ann N Y Acad Sci. 2000;899:136–147.PubMedCrossRefGoogle Scholar
  34. 34.
    Møller P. The alkaline comet assay: towards validation in biomonitoring of DNA damaging exposures. Basic Clin Pharmacol Toxicol. 2006;98:336–345.PubMedCrossRefGoogle Scholar
  35. 35.
    Mortensen PB, Clausen MR. Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand J Gastroenterol Suppl. 1996;216:132–148.PubMedCrossRefGoogle Scholar
  36. 36.
    McCord JM. The evolution of free radicals and oxidative stress. Am J Med. 2000;108:652–659.PubMedCrossRefGoogle Scholar
  37. 37.
    Riedle B, Kerjaschki D. Reactive oxygen species cause direct damage of Englebreth-Holm-Swarm matrix. Am J Pathol. 1997;151:215–231.PubMedGoogle Scholar
  38. 38.
    Martinez CA, Bartocci PC, do Carmo CV, Pereira JA, Miranda DD, Ribeiro ML. The effects of oxidative DNA damage and mutations in the p53 protein on cells of the colonic mucosa with and without the fecal stream: an experimental study in rats. Scand J Gastroenterol. 2010;45:714–724.PubMedCrossRefGoogle Scholar
  39. 39.
    Longatti TS, Acedo SC, de Oliveira CC, et al. Inflammatory alterations in excluded colon in rats—a comparison with chemically-induced colitis. Scand J Gastroenterol. 2010;45:315–324.PubMedCrossRefGoogle Scholar
  40. 40.
    Triantafillidis JK, Nicolakis D, Mountaneas G, et al. Treatment of diversion colitis with 5-aminosalicylic acid enemas: comparison with betamethasone enemas. Am J Gastroenterol. 1991;86:1552–1553.PubMedGoogle Scholar
  41. 41.
    Tripodi J, Gorcey S, Burakoff R. A case of diversion colitis treated with 5-aminosalicylic acid enemas. Am J Gastroenterol. 1992;87:645–647.PubMedGoogle Scholar
  42. 42.
    Song M, Xia B, Li J. Effects of topical treatment of sodium butyrate and 5-aminosalicylic acid on expression of trefoil factor 3, interleukin 1beta, and nuclear factor kappaB in trinitrobenzene sulphonic acid induced colitis in rats. Postgraduat Med J. 2006;82:130–135.CrossRefGoogle Scholar
  43. 43.
    Ancha HR, Kurella RR, McKimmey CC, et al. Luminal antioxidants enhance the effects of mesalamine in the treatment of chemically induced colitis in rats. Exp Biol Med (Maywood). 2008;233:1301–1308.CrossRefGoogle Scholar
  44. 44.
    Ancha HR, Kurella RR, McKimmey CC, et al. Effects of N-acetylcysteine plus mesalamine on prostaglandin synthesis and nitric oxide generation in TNBS-induced colitis in rats. Dig Dis Sci. 2009;54:758–766.PubMedCrossRefGoogle Scholar
  45. 45.
    Cortot A, Maetz D, Degoutte E, et al. Mesalamine foam enema versus mesalamine liquid enema in active left-sided ulcerative colitis. Am J Gastroenterol. 2008;103:3106–3114.PubMedCrossRefGoogle Scholar
  46. 46.
    Singh NP, McCoy MT, Tice RR, et al. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res. 1988;175:184–191.PubMedCrossRefGoogle Scholar
  47. 47.
    Agarwal VP, Schimmel EM. Diversion colitis: a nutritional deficiency syndrome? Nutr Rev. 1989;47:257–261.PubMedCrossRefGoogle Scholar
  48. 48.
    Keshavarzian A, Morgan G, Sedghi S, Gordon JH, Doria M. Role of reactive oxygen metabolites in experimental colitis. Gut. 1990;31:786–790.PubMedCrossRefGoogle Scholar
  49. 49.
    Sousa MV, Priolli DG, Portes AV, et al. Evaluation by computerized morphometry of histopathological alterations of the colon wall in segments with and without intestinal transit in rats. Acta Cir Bras. 2008;23:417–424.PubMedCrossRefGoogle Scholar
  50. 50.
    Nonose R, Spadari APP, Priolli DG, et al. Tissue quantification of neutral and acid mucins in the mucosa of the colon with and without fecal stream: experimental study in rats. Acta Cir Bras. 2009;24:267–275.PubMedCrossRefGoogle Scholar
  51. 51.
    Miyashi Y, Yoshioka A, Iamamura S, et al. Effect of sulphasalazine and its metebolites on the generation of reactive oxygen species. Gut. 1987;28:190–195.CrossRefGoogle Scholar
  52. 52.
    Conner E, Brand S, Davis J, et al. Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease: toxins, mediators, and modulators of gene expression. Inflamm Bowel Dis. 1996;2:133–147.CrossRefGoogle Scholar
  53. 53.
    Naito Y, Takagi T, Yoshikawa T. Neutrophil-dependent oxidative stress in ulcerative colitis. J Clin Biochem Nutr. 2007;41:18–26.PubMedCrossRefGoogle Scholar
  54. 54.
    Simmonds NJ, Allen RE, Stevens TRJ, et al. Chemiluminescence assay of mucosal reactive metabolities in inflammatory bowel disease. Gastroenterology. 1992;103:186–196.PubMedGoogle Scholar
  55. 55.
    Millar AD, Rampton DS, Chander CL, et al. Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut. 1996;39:407–415.PubMedCrossRefGoogle Scholar
  56. 56.
    Guijarro LG, Mate J, Gisbert JP, et al. N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis: randomized, placebo-controlled pilot study. World J Gastroenterol. 2008;14:2851–2857.PubMedCrossRefGoogle Scholar
  57. 57.
    Nikfar S, Rahimi R, Rezaie A, et al. A meta-analysis of the efficacy of sulfasalazine in comparison with 5-aminosalicylates in the induction of improvement and maintenance of remission in patients with ulcerative colitis. Dig Dis Sci. 2009;54:1157–1170.PubMedCrossRefGoogle Scholar
  58. 58.
    Ikeda I, Ominoto A, Wada K, et al. 5-aminosalicylic acid given in the remission stage of colitis suppresses colitis-associated cancer in a mouse colitis model. Clin Cancer Res. 2007;13:6527–6531.PubMedCrossRefGoogle Scholar
  59. 59.
    Ribeiro ML, Priolli DG, Miranda DDC, et al. Analysis of oxidative DNA damage in patients with colorectal cancer. Clin Colorectal Cancer. 2008;7:267–272.PubMedCrossRefGoogle Scholar
  60. 60.
    Siddiqui A, Ancha H, Tedesco D, et al. Antioxidant therapy with N-acetylcysteine plus mesalamine accelerates mucosal healing in a rodent model of colitis. Dig Dis Sci. 2006;51:698–705.PubMedCrossRefGoogle Scholar
  61. 61.
    Aslan A, Temiz M, Atik E, et al. Effectiveness of mesalamine and propolis in experimental colitis. Adv Ther. 2007;24:1085–1097.PubMedCrossRefGoogle Scholar
  62. 62.
    dos Reis SB, de Oliveira CC, Acedo SC, et al. Attenuation of colitis injury in rats using Garcinia cambogia extract. Phytother Res. 2009;23:324–329.PubMedCrossRefGoogle Scholar
  63. 63.
    Seril DN, Liao J, Yang GY, Yang CS. Oxidative stress and ulcerative-associated carcinogenesis: studies in humans and animal models. Carcinogenesis. 2003;24:353–362.PubMedCrossRefGoogle Scholar
  64. 64.
    Wentzel JF, Gouws C, Huysamen C, DyK EV, Koekemoer G, Pretorius PJ. Assessing the DNA methylation status of single cells with comet assay. Anal Biochem. 2010 Feb 13 [Epub ahead of print].Google Scholar
  65. 65.
    Naganuma M, Iwao Y, Ogata H, et al. Measurement of colonic mucosal concentrations of 5-aminosalicylic acid is useful for estimating its therapeutic efficacy in distal ulcerative colitis: comparison of orally administered mesalamine and sulfasalazine. Inflamm Bowel Dis. 2001;7:221–225.PubMedCrossRefGoogle Scholar
  66. 66.
    Lakatos PL, Lakatos L. Ulcerative proctitis: a review of pharmacotherapy and management. Expert Opin Pharmacother. 2008;9:741–749.PubMedCrossRefGoogle Scholar
  67. 67.
    Marshall JK, Irvine EJ. Putting rectal 5-aminosalicylic acid in its place: the role in distal ulcerative colitis. Am J Gastroenterol. 2000;95:1628–1636.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Caroline Caltabiano
    • 1
    • 4
  • Felipe Rodrigues Máximo
    • 2
    • 5
  • Ana Paula Pimentel Spadari
    • 2
    • 5
  • Daniel Duarte da Conceição Miranda
    • 3
    • 6
  • Marcia Milena Pivatto Serra
    • 1
    • 6
  • Marcelo Lima Ribeiro
    • 1
    • 6
  • Carlos Augusto Real Martinez
    • 1
    • 7
  1. 1.Post-Graduate Program in Health SciencesSão Francisco University Medical SchoolBragança PaulistaBrazil
  2. 2.São Francisco University Medical HospitalBragança PaulistaBrazil
  3. 3.São Francisco University Medical SchoolBragança PaulistaBrazil
  4. 4.Vila São Francisco, São PauloBrazil
  5. 5.São José dos CamposBrazil
  6. 6.Bragança PaulistaBrazil
  7. 7.Santo AndréBrazil

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